Loonen Anton J M
Unit of PharmacoTherapy, -Epidemiology & -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713AV, Groningen, the Netherlands.
Brain Behav Immun Health. 2023 Sep 23;33:100687. doi: 10.1016/j.bbih.2023.100687. eCollection 2023 Nov.
The term extrapyramidal disorders is most often used for conditions such as Parkinson's disease or Huntington's disease, but also refers to a group of extrapyramidal side effects of antipsychotics (EPS), such as tardive dyskinesia (TD). After a brief description of some clinical features of TD, this article summarizes the relatively scarce results of research on a possible link between mainly cytokine levels and TD. This data was found by systematically searching Pubmed and Embase. The limitations of these types of studies are a major obstacle to interpretation. After describing relevant aspects of the neuroinflammatory response and the neuroanatomical backgrounds of EPS, a new hypothesis for the origin of TD is presented with emphasis on dysfunctions in the striosomal compartment of the striatum and the dorsal diencephalic connection system (DDCS). It is postulated that (partly immunologically-induced) increase in oxidative stress and the dopamine-dependent immune response in classic TD proceed primarily via the DDCS, which itself is activated from evolutionarily older parts of the forebrain. Neuroinflammatory responses in the choroid plexus of the third ventricle may contribute due to its proximity to the habenula. It is concluded that direct evidence for a possible role of inflammatory processes in the mechanism of TD is still lacking because research on this is still too much of a niche, but there are indications that warrant further investigation.
锥体外系疾病这一术语最常用于帕金森病或亨廷顿病等病症，但也指抗精神病药物的一组锥体外系副作用（EPS），如迟发性运动障碍（TD）。在简要描述TD的一些临床特征后，本文总结了关于主要细胞因子水平与TD之间可能联系的相对较少的研究结果。这些数据是通过系统检索PubMed和Embase找到的。这类研究的局限性是解释的主要障碍。在描述神经炎症反应的相关方面和EPS的神经解剖学背景后，提出了一个关于TD起源的新假说，重点是纹状体的纹状小体区和背侧间脑连接系统（DDCS）的功能障碍。据推测，经典TD中氧化应激和多巴胺依赖性免疫反应的（部分由免疫诱导的）增加主要通过DDCS进行，而DDCS本身是由前脑进化上较古老的部分激活的。第三脑室脉络丛中的神经炎症反应可能因其与缰核的接近而有所贡献。结论是，由于对此的研究仍过于小众，炎症过程在TD机制中可能作用的直接证据仍然缺乏，但有迹象表明值得进一步研究。
